Lifelong imbalanced LA/ALA intake impairs emotional and cognitive behavior via changes in brain endocannabinoid system

Abstract

Imbalanced dietary n-3 and n-6 PUFA content has been associated with a number of neurological conditions. Endocannabinoids are n-6 PUFA derivatives, whose brain concentrations are sensitive to modifications of fatty acid composition of the diet and play a central role in the regulation of mood and cognition. As such, the endocannabinoid system appears to be an ideal candidate for mediating the effects of dietary fatty acids on mood and cognition. Lifelong administration of isocaloric α-linolenic acid (ALA)-deficient and -enriched diets induced short-term memory deficits, whereas only dietary ALA enrichment altered emotional reactivity in adult male rats compared with animals fed a standard diet that was balanced in ALA/linoleic acid (LA) ratio. In the prefrontal cortex, both diets reduced 2-AG levels and increased MAG lipase expression, whereas only the enriched diet reduced AEA levels, simultaneously increasing FAAH expression. In the hippocampus, an ALA-enriched diet decreased AEA content and NAPE-PLD expression, and reduced 2-AG content while increasing MAG lipase expression. These findings highlight the importance of a diet balanced in fatty acid content for normal brain functions and to support a link between dietary ALA, the brain endocannabinoid system, and behavior, which indicates that dietary ALA intake is a sufficient condition for altering the endocannabinoid system in brain regions modulating mood and cognition

Targeted Lipidomics Investigation of N‐acylethanolamines in a Transgenic Mouse Model of AD: A Longitudinal Study

“…NAEs were extracted from brain areas and plasma and then quantified as previously reported . In brief, plasma and brain areas were dounce‐homogenized and extracted with chloroform/methanol/Tris‐HCl (50 mM, pH 7.4) (2:1:1, v/v) containing internal deuterated standards for PEA, OEA, AEA, and DHEA quantification by isotope dilution [d4‐PEA, d4‐OEA, d8‐AEA, and d4‐DHAEA (Cayman Chemical)], as well as 17:0‐AE (Cayman Chemical) for EPEA measurement.…”

Lactational changes of fatty acids and fat-soluble antioxidants in human milk from healthy Chinese mothers

“…Since n-6 series-derived eicosanoids are associated with proinflammatory properties, the predominance of n-6 PUFA is suggestive of higher risks of childhood allergic diseases, such as asthma and atopic eczema (9,15) . Also, the imbalance between n-6 and n-3 PUFA has been correlated with impaired cognitive and emotional development via epoxy metabolites and endocannabinoid system (12,13,36) . More investigations are warranted to confirm whether the increasing ratio of LA:ALA or n-6:n-3 PUFA in human milk is harmful to the short-term and long-term health of human infants.…”

“…balance and neocortical development (9,12,13) . Contrarily, n-3 LC-PUFA help in promoting psychomotor development and lowering the risk of lifelong allergic diseases and emotional problems (8,12,14,15) .…”

Endogenous omega-3 long-chain fatty acid biosynthesis from alpha-linolenic acid is affected by substrate levels, gene expression, and product inhibition

“…14,30 Moreover, many desaturase genes participate in the synthesis of u-3 LC-PUFAs from the precursor essential PUFAs, 31 such as LA and ALA, which share the same enzyme system. 16,32 Our data demonstrated that the expression of lipogenic enzymes could be affected by different dietary levels of ALA (Fig. 3).…”